Hypophosphatemia accompanied by a decline in red blood cell 2,3 disphosphoglyceric acid (2,3-DPG) has been known for many years to occur during the therapy of diabetic ketoacidosis (DKA). Because low 2,3-DPG levels produce a shift in the oxyhemoglobin dissociation curve (p50) to the left, potentially causing tissue hypoxia, some investigators have advocated the routine use of phosphate salts in the therapy of DKA. Controversy continues concerning this, however, since hypocalcemia and hypomagnesmia have been reported following phosphate infusions during DKA. The present study was designed to demonstrate the effect of phosphate therapy in DKA patients in a randomized prospective protocol. Upon admission to the Clinical Research Center, patients are randomly assigned either to receive phosphate or not, all other treatment modalities including insulin, total fluid replacement, potassium, and other supportive procedures being maintained as similar as possible for both groups. Serum phosphate, erythrocyte 2,3-DPG, p50, electrolytes, calcium, ionized calcium, and magnesium are measured serially during the course of treatment. Studies to date have demonstrated that phosphate therapy during the first 24 hours of treatment can significantly elevate serum phosphate levels with an associated rise in RBC 2,3-DPG and p50. During the next grant year, it is anticipated that a sufficient number of additional subjects will be investigated to determine if there is statistical significance in these observations.